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Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.

Li FF, Zhu SQ, Wang SZ, Gao C, Huang SZ, Zhang M, Ma X - Mol. Vis. (2008)

Bottom Line: All members were genotyped with microsatellite markers at loci previously associated with cataracts.This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail.

Methods: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC).

Results: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.

Conclusions: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

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Related in: MedlinePlus

Denaturing high-performance liquid chromatography results of wild type and mutated CRYBB2. DHPLC results show variant traces for CRYBB2 compared with the wild type (WT) trace. The profile in blue is the mutant protein; the profile in red is the wild type protein.
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f4: Denaturing high-performance liquid chromatography results of wild type and mutated CRYBB2. DHPLC results show variant traces for CRYBB2 compared with the wild type (WT) trace. The profile in blue is the mutant protein; the profile in red is the wild type protein.

Mentions: Denaturing HPLC analysis confirmed this mutation (Figure 4), which cosegregated with all affected individuals in the family. Further, this mutation was not observed in any of the unaffected family members or the 100 normal controls.


Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.

Li FF, Zhu SQ, Wang SZ, Gao C, Huang SZ, Zhang M, Ma X - Mol. Vis. (2008)

Denaturing high-performance liquid chromatography results of wild type and mutated CRYBB2. DHPLC results show variant traces for CRYBB2 compared with the wild type (WT) trace. The profile in blue is the mutant protein; the profile in red is the wild type protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2335123&req=5

f4: Denaturing high-performance liquid chromatography results of wild type and mutated CRYBB2. DHPLC results show variant traces for CRYBB2 compared with the wild type (WT) trace. The profile in blue is the mutant protein; the profile in red is the wild type protein.
Mentions: Denaturing HPLC analysis confirmed this mutation (Figure 4), which cosegregated with all affected individuals in the family. Further, this mutation was not observed in any of the unaffected family members or the 100 normal controls.

Bottom Line: All members were genotyped with microsatellite markers at loci previously associated with cataracts.This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail.

Methods: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC).

Results: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.

Conclusions: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

Show MeSH
Related in: MedlinePlus